Gastrointestinal Neoplasms 

Primary GI neoplasms in children are rare entities. In 1960, the incidence of GI malignancies arising from the bowel was estimated at less than 1% of pediatric tumors. Most of these diagnoses were made during urgent exploration for an abdominal crisis; this is in contrast to adults, in whom 22% of malignancies are located in the GI tract; furthermore, most adults have long-standing symptoms such as pain, weight loss, and bleeding. As with other pediatric cancers, those of the GI tract differ from those in adults in terms of histology, pathogenesis, and clinical presentation.^[1]

Much of the pediatric literature regarding GI malignancies consists of case reports. Consequently, this article focuses on the more common benign and malignant neoplasms of the GI tract in children, in addition to information gleaned from fairly sparse literature.

Benign and malignant smooth muscle tumors of the esophagus in children account for fewer than 5% of all the leiomyomas and leiomyosarcomas. Tumors in the pediatric population, in contrast to those in adults, are multiple; localized tumors represent only 9% of cases. In children, these tumors are more commonly found in girls than in boys. Presenting symptoms include dysphagia, retained food, and chest pain. Barium swallow reveals proximal dilation that is easily confused with achalasia. Esophagoscopy reveals a mucosal-covered narrowing; biopsy is diagnostic. The treatment for symptomatic lesions is surgical resection, which often requires esophageal replacement because of the diffuse nature of the disease. One series reports only 11% of leiomyomas were amenable to enucleation.

Children with long-standing gastroesophageal reflux disease are at risk for developing Barrett esophagus, dysplasia, and adenocarcinoma in a progression similar to adults.^[2] In one reflux series, 13% of children having surveillance endoscopy and biopsy were found to have Barrett esophagus. Fewer than 200 pediatric cases of Barrett esophagus are reported in the literature; thus, surveillance and treatment are based on adult recommendations. Every patient needs aggressive medical treatment. Cases that have advanced to metaplasia should be seriously considered for antireflux procedures. High-grade dysplasia or adenocarcinoma of the esophagus requires esophagectomy and gastric pull-up or bowel interposition for reconstruction.

Gastric teratomas comprise less than 1% of all childhood teratomas. Clinical presentation generally occurs within the first 3 months of life as an abdominal mass, abdominal distention, emesis, GI bleeding, anemia, and respiratory distress. Teratomas in this location occur predominantly in males (96%); no cases of malignant transformation have been reported. Diagnosis is made with ultrasonography and/or CT scanning, which reveal the characteristic heterogenous appearance, including fat, calcifications, and cystic areas. Most cases are treated with simple resection (see the image below), but partial gastrectomy may be necessary.

Gastric carcinoma accounts for only 0.05% of GI malignancies in childhood. Symptoms are often similar to peptic ulcer disease and include pain and vomiting. The diagnosis is made by upper endoscopy with biopsy or upper GI contrast series. Because of the rarity of this lesion, current recommendations for therapy are based on the adult literature. The first step is to determine if the child is an operative candidate, and CT scanning and intraesophageal ultrasonography both are useful in determining the extent of disease. Complete or partial gastrectomy may be performed with resection of surrounding lymph nodes; however, overall prognosis is poor. Surgical resection with or without concomitant chemotherapy and radiation may prolong survival, but the mortality rate remains high.

Lymphoma is the most common small bowel malignancy in the pediatric age group. In one of the larger series, non-Hodgkin lymphomas (NHLs) comprised 74% of alimentary tract malignancies.^[3] Tumors were found in the colon (50.9%), small bowel (21.8%), and stomach (1.8%). Many other series identify 50-93% of patients who have primary intestinal lymphomas located in the ileocecal region. See the image below.

The most common histologic subtype of these tumors is Burkitt lymphoma, which accounts for up to 75% of the lesions. Correct preoperative diagnosis rarely occurs, and laparotomy with tissue evaluation is used for diagnosis. Patients generally have a history of nonspecific chronic abdominal pain and present urgently with an acute exacerbation caused by intussusception (46%), appendicitis (22%), perforation (11%), or bowel obstruction (8%). Physical examination may reveal occult blood per rectum and/or a palpable abdominal mass. If the diagnosis is made preoperatively, a bone marrow biopsy is performed to rule out metastatic disease. Otherwise, this study is required after laparotomy as part of the staging of the lymphomatous disease.

Surgical management of GI NHL depends on the stage of disease at presentation. Tumor burden is the most reliable prognostic factor. Bulky disease can rarely be completely resected, and aggressive debulking has not shown a survival benefit. In these cases, surgery should be limited to evaluating the extent of disease and obtaining adequate tissue for diagnosis, followed by intense multiagent chemotherapy. In cases of localized disease, complete surgical resection includes removal of the primary tumor and thorough examination of mesenteric lymph nodes, liver, and para-aortic lymph nodes to assess for metastatic disease. Complete surgical resection is followed by a histopathologically specific chemotherapy protocol, but the duration and intensity of therapy is decreased because the stage is lower.

Carcinoid tumors are derived from enterochromaffin cells located throughout the GI tract. Overall, carcinoids are most commonly found in the ileum (30%), appendix (30%), and, less frequently, in the remaining intestine. Enterochromaffin cells are not usually present in the GI tract until after age 4 years; thus, most carcinoids in children occur after age 5 years. The yearly incidence of carcinoid tumors occurring in children aged 10-15 years is 0.4-0.8 per 100,000 population.

Most children present with symptoms of acute appendicitis, which are likely caused by luminal obstruction by the tumor. Rarely, carcinoids first manifest with carcinoid syndrome, an indication of metastasis to the liver or beyond. This consists of flushing, tachycardia, diarrhea, and asthma secondary to release of serotonin, substance P, or other vasoactive mediators that do not pass through hepatic deactivation before entering the systemic circulation. In these cases, diagnosis is confirmed by finding elevated urinary levels of 5-hyroxyindoleacetic acid (5-HIAA), which is a metabolite of serotonin. If 5-HIAA is elevated, further localization of the tumor is possible using computed tomography scanning or magnetic resonance imaging.

Appendiceal carcinoids are almost never metastatic, but 70% of ileal and cecal carcinoids metastasize. The distinction between benign and malignant tumors is the presence of metastasis rather than histologic features. The treatment of appendiceal carcinoids is simple appendectomy if the lesion is smaller than 2 cm. Tumors larger than 2 cm have a higher frequency of metastasis and are treated with a right hemicolectomy. Treatment of small bowel carcinoids requires wide resection and regional lymph node sampling. At the time of surgery, an intense yellow appearance aids in the diagnosis, and care is taken during surgery because carcinoid crisis can occur from sudden release of vasoactive mediators. The overall survival rate in children is excellent, especially for the common smaller (< 2 cm) carcinoids of the appendix.

Juvenile polyps, as shown below, are the most common type of neoplasm in the GI tract, comprising 80% of polyps in children. Grossly, the polyps appear beefy red and range in diameter from several millimeters to several centimeters. Histologically, these lesions represent benign hamartomas and have no malignant potential. They commonly manifest as painless rectal bleeding in toddlers but may manifest with prolapse (4%) or abdominal pain (10%).

Diagnosis is made through a thorough history, rectal examination, sigmoidoscopy, colonoscopy, and/or a contrast enema (generally an air/contrast enema); see the image below. Polyps in the distal colon and rectum are easily resected via endoscopic polypectomy. More proximal lesions are resected endoscopically, rarely with colotomy and polypectomy, or left to spontaneously slough if adequate visualization of the entire colon demonstrates fewer than 5 polyps, thus excluding the diagnosis of juvenile polyposis syndromes. If 5 or more polyps are identified, complete excision of all polyps is preferred, either via colonoscopy or surgical excision with multiple enterotomies for less accessible lesions. This eliminates the problem and yields tissue to correctly characterize the polyp type.

Juvenile polyposis syndrome is a dominantly inherited disorder that can occur as diffuse juvenile polyposis of infancy (0-3 mo), diffuse juvenile polyposis (6 mo to 5 y), and juvenile polyposis coli (5-15 y). Presenting signs include diarrhea, rectal bleeding, intussusception, anemia, prolapse, and failure to thrive. The diagnosis is made using the same diagnostic modalities discussed above, and the presence of 5 or more polyps in sporadic cases or one polyp in cases with a family history confirms the diagnosis. These children are at high risk for malignancy (17%) occurring by the fourth decade of life and need long-term surveillance. Many surgeons recommend prophylactic colectomy and rectal mucosectomy with endorectal pull-through as the primary treatment for this disease as soon as the diagnosis is established.

Peutz-Jegher syndrome is another autosomal dominant disease and is characterized by the presence of intestinal polyps with mucocutaneous pigmentation of the mouth, hands, and feet. The polyps may be found anywhere from the stomach to the rectum, with most occurring in the small bowel. The polyps are classified as hamartomas of the muscularis mucosa. Patients without a family history often present with cramping abdominal pain caused by intermittent intussusception of a polyp. These patients have an increased risk of cancer with transformation of hamartomas into carcinomas. Extraintestinal tumors are also associated with this syndrome and include ovarian, cervical, and testicular cancers.

Diagnosis of Peutz-Jegher syndrome is made by family history, pigmented spots, and cramping abdominal pain. Current recommendations for treatment are annual physical examinations, CBC count, breast and pelvic examinations, testicular examinations with ultrasonography, and pancreatic ultrasonography. Esophagogastroduodenoscopy (EGD) and colonoscopy are recommended every 6 months. Polyps larger than 5 mm are removed during colonoscopy. Small bowel polyps larger than 1.5 cm are surgically resected, using intraoperative endoscopy, if necessary, for localization.

Familial adenomatous polyposis (FAP) is an autosomal dominant cancer predisposition syndrome characterized by more than 100 visible adenomatous polyps in the colon. It is caused by germ-line mutations in the adenomatous polyposis coli (APC) gene. Patients present with rectal bleeding, anemia, abdominal pain, or diarrhea. Most cases are diagnosed based on routine screening of children from an affected family. Increasingly, at-risk patients can be identified with molecular diagnostics (ie, screening for APC gene mutations). Diagnosis is established by sigmoidoscopy, which reveals a colon carpeted with polyps. Polyps occur anywhere along the GI tract, but most of the adenomatous polyps are in the colon. The risk for developing malignancy is 100%. Therefore, surgical resection of the entire colon is necessary. See the images below.

The most common operation performed for FAP has been total abdominal colectomy with ileorectal anastomosis. This requires frequent surveillance of the rectal stump. More recently, total colectomy with rectal mucosectomy and endorectal ileal pull-through has become the standard of care at many institutions. Annual upper and lower endoscopy is recommended in all patients. Resection of remaining polyps should be performed for polyps larger than 1 cm, rapidly enlarging polyps, or polyps with severe dysplasia.

Gardner syndrome is an autosomal dominant disorder described as the association between colonic familial adenomatous polyposis and multiple osteomas, fibromas, and epidermoid cysts. The natural history and treatment of the colonic polyps mimics that for patients with familial adenomatous polyposis. Turcot syndrome is the association of colonic familial adenomatous polyposis and brain tumors.

Lymphoid polyps are pseudopolyps of submucosal intestinal lymphatic tissue secondary to hyperplasia due to nonspecific infectious causes. These polyps may ulcerate and erode the overlying mucosa, bleed, and cause chronic anemia. Colonoscopy and/or contrast enemas are the diagnostic modalities of choice. The appearance by either technique shows a morphologic distinction from juvenile or adenomatous polyps. No treatment is necessary, and therapy is directed towards eradicating the underlying infectious process.

Colorectal carcinoma is the most common colonic malignancy in children and occurs with an incidence of 1.3-2 cases per million population. Predisposing factors are noted in 10-25% of childhood colorectal cancers, and the rest arise spontaneously. The 2 main premalignant conditions giving rise to colorectal cancers are polyposis syndromes and inflammatory bowel disease.

The risk of developing adenocarcinoma of the colon or rectum in ulcerative colitis is 3% during the first 10 years of disease, and this increases 10-15% in each subsequent decade. Patients with Crohn disease have a cancer risk 20 times higher than the general population and require regular surveillance and random biopsies.

In the sporadic type of colorectal cancers, the predominant histologic type appears to be mucinous adenocarcinoma (as shown below), occurring in up to 80% of patients. Mucinous adenocarcinoma is associated with the worst prognosis. Children present with nonspecific abdominal symptoms, including cramping abdominal pain, vomiting, and rectal bleeding. Workup includes barium enema, colonoscopy, and CT scanning.

Most children with mucinous adenocarcinoma present with advanced disease secondary to delay in diagnosis. In one of the larger series, because of the predominantly aggressive mucinous histology, complete resection was achieved in only 30% of children. Surgery with the intent to cure consists of a radical resection of the portion of colon involved, its mesentery, and the surrounding lymphatics. Palliative therapy includes permanent colostomy to relieve obstruction. Adjuvant chemotherapy and radiation are used, but very little survival benefit has been demonstrated. The 5-year survival rate ranges from 5-28%, and this directly correlates with the completeness of resection.